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Effects of oral administration of levamisole on non-specific immunity, serum proteins and health in normal colostrum-fed neonatal dairy calves

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Soon after levamisole became widely used as a veterinary anthelmintic, it was recognised that concurrent enhancement of immune responsiveness sometimes accompanied anthelmintic treatment, especially in old or chronically ill animals. There are many reports concerning the immunomodulatory effects of levamisole in immunocompromised and vaccinated animals, but information about the effects of levamisole in immunocompetent animals is limited and controversial. Thirty Holstein dairy calves were randomly divided into two groups: test (n=15) and control (n=15). Blood samples were taken from the jugular vein, between 24h and 48h after birth, and put into EDTA-containing tubes and plain tubes; levamisole was then administrated orally at a dose of 2mg/kg body weight three times at 1-day intervals in test groups. Blood sampling from all the calves was continued at days 7, 14, 21 and 28. The weight of calves was measured only at days 1 and 28 (before feeding). The levels of packed cell volume (PCV) (microhaematocrit), total white blood cells (WBCS) and differential leukocyte count (manual standard methods), total serum protein (colorimetry), beta and gamma globulins (electrophoresis), albumin:globulin (A:G) (calculated) and disease occurrence were measured and recorded. Appropriate statistical methods were used for data analysis, and P0.05 was considered as significant. No significant differences were seen for PCV, total serum protein, WBC count and health between groups. In the test group, neutrophil level at day 14 and monocyte level at day 21 were significantly higher than in the control group (PP
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ORIGINAL ARTICLE
M. Mohri Æ H. A. Seifi Æ S. H. Zamani Sani
Effects of oral administration of levamisole on non-specific immunity,
serum proteins and health in normal colostrum-fed neonatal dairy calves
Received: 12 September 2004 / Accepted: 2 November 2004 / Published online: 14 December 2004
Springer-Verlag London Limited 2004
Abstract Soon after levamisole became widely used as a
veterinary anthelmintic, it was recognised that concur-
rent enhancement of immune responsiveness sometimes
accompanied anthelmintic treatment, especially in old or
chronically ill animals. There are many reports con-
cerning the immunomodulatory effects of levamisole in
immunocompromised and vaccinated animals, but
information about the effects of levamisole in immuno-
competent animals is limited and controversial. Thirty
Holstein dairy calves were randomly divided into two
groups: test (n=15) and control (n=1 5). Blood samples
were taken from the jugular vein, between 24 h and 48 h
after birth, and put into EDTA-containing tubes and
plain tubes; levamisole was then administrated orally at
a dose of 2 mg/kg body weight three times at 1-day
intervals in test groups. Blood sampling from all the
calves was continued at days 7, 14, 21 and 28. The
weight of calves was measured only at days 1 and 28
(before feeding). The levels of packed cell volume (PCV)
(microhaematocrit), total white blood cells (WBCS) and
differential leukocyte count (manual standard methods),
total serum protein (colorimetry), beta and gamma
globulins (electrophoresis), albumin:globulin (A:G)
(calculated) and disease occurrence were measured and
recorded. Appropriate statistical methods were used for
data analysis, and P £ 0.05 was considered as signifi-
cant. No significant differences were seen for PCV, total
serum protein, WBC count and health between groups.
In the test group, neutrophil level at day 14 and
monocyte level at day 21 were significantly higher than
in the control group (P<0.05). Electrophoresis showed
no significant differences for beta globulin level and A:G
between groups, but gamma globulin level at day 28 was
significantly higher in the test group (P<0.05).
Keywords Dairy calves Æ Health Æ Leukogram Æ
Levamisole Æ Se rum proteins
Introduction
Levamisole is a highly acceptable anti-nematodal drug
because of its broad range of activity in a large number
of hosts (sheep, cattle, horse, pig, dog, chicken). Soon
after tetramisole and, subsequently, levamisole became
widely used as veterinary anthelmintics, it was recognised
that concurrent enha ncement of immune responsiveness
sometimes accompanied anthelmintic treatment, espe-
cially in old or chronically ill animals (Courtney and
Roberson 1995).
The high mortality of infant cattle, horse, sheep and
pigs has been a serious problem in farm animal breeding
for many years. Such losses are mostly caused by
infectious diseases, especially in the neonatal and post-
natal periods.
Intensive studies have recently been initiated to assess
methods of preventing and treating infectious diseases.
One of these methods has been non-specific immuno-
prophylaxis with natural or synthetic immunomodula-
tors. Successful results have already been obtained in the
prophylaxis of diseases of young farm animals after non-
specific stimulation of the pregnant adults (Deshpande
et al. 1991; Kotowski 1991; Krakowski et al. 1999;
Wawron and Szczubial 2000).
These immunologically enhancing treatments sug-
gested that the drug might be of value in promoting cell-
mediated and humoral immunity in neonatal dairy
calves. Most previous reports studied the effects of lev-
amisole administration on immunocompromised or
vaccinated animals (Irwin et al. 1976; Babiuk and Misra
1981, 1982; Roth and Kaeberle 1984; Ivanov et al. 1987;
Ogunbiyi et al. 1988; Sharma et al. 1990), but there are
M. Mohri (&) Æ H. A. Seifi Æ S. H. Zamani Sani
Department of Clinical Sciences,
School of Veterinary Medicine,
Ferdowsi University of Mashhad,
91775-1793, Mashhad, Iran
E-mail: mohri@ferdowsi.um.ac.ir
Tel.: +98-511-6610430
Fax: +98-511-6620166
Comp Clin Path (2005) 13: 132–136
DOI 10.1007/s00580-004-0528-0
limited data concerning the effects of orally administered
levamisole in normal immunocompetent neonatal
calves. The present study was performed to reveal the
effects of levamisole on leukogram, globulin levels and
health in normal colostrum-fed neonatal dairy calves.
Materials and methods
The study was conducted in a da iry herd with approxi-
mately 400 calves per year at Mashhad suburb (north-
east of Iran). This herd consisted of pure-bred animals
of the Holstein breed. The herd was totally confined in
free-stall housing without access to pasture. Cows were
fed with alfalfa hay, concentrate and corn silage.
The cows were dried 2 months before their expected
time of parturition and transferred to a separate stall. As
the time of parturition approached, they were moved to
straw-bedded maternity pens. Prompt assistance was
given to cows with dystocia. Following parturition the
umbilicus of each calf was treated with pavidone iodine,
and the calf was weighed and transferred to an indi-
vidual pen. Within the first 6 h of life 2.5 kg of the dam’s
colostrum was bottle-fed to the calf, and colostrum
feeding was cont inued every 12 h for 48 h. After 48 h
herd milk was used for feeding twice daily (2 kg every
12 h) until the calf was 10 days old. After this time
concentrate, high quality alfalfa and water were allowed
ad libitum. The calves were weaned at 45 days of age.
The heifer calves were mainly used as herd replacements.
Thirty calves were used in the present study. They
were divided into two groups (test n=15; control n=15).
Based on the gender and parity of dams, the number of
calves in each group was approximately identical. In the
test group oral levamisole was administered at a dose of
2 mg/kg body weight three times at 1-day intervals.
Samples were taken from the jugular vein between 24 h
and 48 h after birth (before levamisole administration in
the test group) and on days 7, 14, 21 and 28. The blood
was added to EDTA-containing tubes for haematologi-
cal measurements and plain tubes for serum extraction
and measurement of total protein and serum protein
electrophoresis. The serum was harvested after centri-
fugation at 3,000 rpm for 10 min and stored at 20C
until required for analysis.
The haematocrit [packed cell volume (PCV)] levels
were obtained by microhaematocrit methods. White
blood cell (WBC) measurements were taken manually by
standard methods (Dacie and Lewis 1984). Differential
leukocyte counts were performed on routinely prepared
Giemsa-stained blood films by the cross-sectional tech-
nique (Jain 1986). One hundred leukocytes were identi-
fied. Serum total protein was determined by Biuret
colorimetric method with a spectrophotometer (Jenway
6105, Jenway, Felstead, England). Percentage and
absolute levels of beta and gamma globulins were
determined by cellulose acetate electrophoresis and
densitometry (Helena system). Disease occurrence was
also recorded during the experiment.
The SAS program was used for data analysis. After
testing normal distributions of the data we used a
parametric independent t-test to investigate significant
difference between groups at various sampling times.
The chi-square test was also used for comparison of
disease occurrence between groups. P £ 0.05 was con-
sidered as signific ant.
Results
The results are shown in Tables 1 and 2. No significant
differences were seen for PCV, total serum protein and
WBC count between groups. In the test group, neutro-
phil level at day 14 and monocyte level at day 21 were
significantly higher than the control group (P<0.05).
Electrophoresis showed no significant differences for
beta globulin level and albumin:globulin (A:G) between
groups but gamm a globulin level at day 28 was sig-
nificantly higher in the test group (P<0.05).
During the study, in the test group, six cases of
diarrhoea were recorded. In the control group ten cases
of diarrhoea occurred. The chi-square test showed no
significant difference between groups for disease occur-
rence.
Discussion
There are reports concerning the effects of levamisole
administration on the immune response of various ani-
mal species (Hunter et al. 1981; Singh and Dhawedkar
1993; Sopinska and Guz 1993; Wisniewski et al. 1993;
Asif et al. 1995; Cabaj et al. 1995; Keskar et al. 1996;
Findly and Munday 2000; Qureishi et al. 2000; Zia-ul-
Rahman et al. 2003). For calves, most of the papers
studied the immunomodulatory effects of simultaneous
administration of levamisole and various vaccines.
However, the information about the effects of levamisole
in normal intact neonatal dairy calves is limited and
controversial.
There are few reports concerning the alterations of
leukocyte number after levamisole administration. Asif
et al. (1995) reported no significant changes in the
leukocyte, neutrophil, eosinophil and basophil counts in
Sahiwal heifers after oral administration of levamisole.
In another study on buffalo heifers, Zia-ul-Rahman et al.
(2003) reported an increase of WBCs on day 1 after
levamisole administration, which returned to pre-dose
levels at 7 and 14 days after dosing. Neutrophil per-
centage decreased and lymphocyte percentage increased
on days 7 and 14 after drug administration, but an
increase in monocyte count was observed on days 7 and
14 of the experiment. Our results are consisten t with
those of Asif et al. (1995) and Zia-ul-Rahman et al.
(2003), with regard to WBC count, and Zia-ul-Rahman
et al. (2003) for monocyte level. Paulik et al. (1992)
showed increased levels of neutrophil percentage in
mice after levamisole administration. Nalini-Kumari and
133
Choudhuri (1986) have studied the levamisole effects,
together with rinderpest vaccinat ion, in buffalo calves.
They reported a non-significant increase in leukocyte
count, with significant increase in lymphocyte percentage
that was associated with a decrease in the neutrophil le-
vel. These changes occurred 1–3 weeks after levamisole
administration. Goranov and Bonovska (1987) reported
no changes in the total count of leukocytes in sheep after
levamisole injection, although a rise in the phagocytic
activity of neutrophils was seen. In the present study
there were significant differences between neutrophil and
monocyte levels at the second and third weeks of the trial
between groups, respectively (P<0.05). These findings
are consistent with those of Paulik et al. (1992) but are
in contrast with the results of Nalini-Kumari and
Choudhuri (1986) and Goranov and Bonovska (1987).
This study revealed significant difference in gamma
globulin levels between groups, with higher values in the
test group (P<0.05). Since most of the im-
munoglobulins migrate in the gamma globulin zone, this
suggests that levamisole administration induced anti-
body production in the test group.
Some apparently conflicting evidence also exists with
regard to the effect of levamisole on antibody produc-
tion. The results of the present study are consistent with
Bekere’s findings (1988), indicating that levamisole given
to neonatal cattle increases the value of humoral factors
of natural immunity, and levamisole could, therefore, be
used for improving the formation of natural immunity
and as a preventive against hypoproteinaemia in new-
born cattle. Zia-ul-Rahman et al. (2003 ) reporte d in-
creased levels of total serum protein on day 7, whereas
globulin increased on days 7 and 14 after levamisole
administration in buffalo heifers. Our results are con-
sistent with those of Zia-ul-Rahman et al. (2003) for
gamma globulin level. The difference between times of
increase is probably related to species difference or dose
and number of administrations. Singla and Juyal (1992)
observed an increase in serum gamma globulin levels in
calves infected with Trypanosoma evansi and in calves
infected with T. evansi and simultaneously treated with
levamisole, but, compared with untreated uninfected
controls, the increase was significant only in the infected/
treated group. Furthermore, there are reports concern-
ing augmented humoral immune responses after lev-
amisole administration following vaccination against
Pasteurella multocida and infectious bovine rhinotra-
cheitis virus in calves and cattle, respectively (Babiuk
and Misra 1982; Sharma et al. 1990). Similar results
were obtained in suckling rats immunised against sheep
red blood cells (Hunter et al. 1981). Sheep given vacci-
nations against clostridial diseases and levamisole had
higher anti-clostridial antibody titres than sheep given
only vaccine (Hogarth-Scott et al. 1980 ). On the other
hand, in a further study, blood derivative containing
10% bovine serum proteins (60% immunoglobulins
and 40% albumin) and 10 mg levamisole per ml, or
levamisole alone, was given i.m. to fifteen 3-week-old
calves at a levamisole dose of 10 mg/kg body weight, the
Table 1 Mean ± SE of some haematological parameters and statistical comparisons between trial groups
Timepoint PCV (%) WBC(10
9
/l) Neutrophils (10
9
/l) Band(10
9
/l) Lymphocytes (10
9
/l) Monocytes (10
9
/l) Eosinophils (10
9
/l)
Test Control Test Control Test Control Test Control Test Control Test Control Test Control
24–48 h 35.11±0.02 33.31±0.01 10.21±1.08 9.74±0.86 6.04±0.59 6.64±0.70 0.000 0.004±0.004 4.04±0.65 2.93±0.26 0.080±0.049 0.086±0.043 0.014±0.006 0.053±0.035
P value 0.76 0.87 0.52 0.4 0.31 0.78 0.38
First week 32.01±0.01 32.11±0.01 8.39±0.74 10.73±1.18 3.44±0.62 5.08±1.02 0.005±0.005 0.006±0.006 4.69±0.32 5.22±0.80 0.081±0.022 0.055±0.025 0.016±0.009 0.011±0.011
P value 0.62 0.28 0.32 0.1 0.74 0.28 0.37
Second week 30.41±0.01 31.00±0.01 8.66±0.98 8.22±0.68 3.74±0.59 2.36±0.50 0.000 0.006±0.006 4.84±0.48 5.53±0.48 0.12±0.044 0.070±0.029 0.000 0.000
P value 0.78 0.98 0.02 0.36 0.32 0.34
Third week 29.81±0.01 29.31±0.01 9.38±0.78 8.18±0.59 2.60±0.42 2.25±0.34 0.000 0.000 6.48±0.48 5.54±0.41 0.17±0.071 0.049±0.043 0.000 0.015±0.009
P value 0.84 0.23 0.07 0.12 0.01 0.09
Fourth week 29.31±0.01 31.11±0.02 10.09±0.91 9.68±0.74 3.63±0.49 3.05±0.43 0.000 0.000 6.39±0.61 6.50±0.41 0.077±0.035 0.10±0.029 0.000 0.000
P value 0.82 0.82 0.39 0.59 0.35
134
dose being repeated 5 days later. Neither preparation
had any effect on humoral immunity (Paulik et al. 1989).
Babiuk and Misra (1981 ) suggested that administration
of levamisole and attenuated infectious bovine rhino-
tracheitis vaccine in vivo did not elevate cellular or hu-
moral responses. Cabaj et al. (1995) reported similar
results in lambs injec ted with human erythrocytes and
ovalbumin 1 day after levamisole administration.
Most drugs’ actions on the immune system are
modulated by the interaction between the T cell
recruiting efficacy of the sulphur moiety and the cho-
linergic effects of the imidazole ring (Renoux 1980).
Levamisole appears to alter cyclic nucleotide phospho-
diesterases, decreasing cyclic guanosine monophosphate
(cGMP) degradation and increasing cyclic adenosine
monophosphate degradation (Boothe 2001). Stogause
and King (1995) suggested that, in the rat, levamisole
administration caused lower levels of corticosterone
than in controls and probably this reduction increased
immune function. Szeto et al. (2000) reported that lev-
amisole induces interleukin 18, a recently characterised
cytokine with potent activity in sti mulating interferon
gamma and shifting the immune balance toward a
type 1 response.
In conclusion our results indicated that, in normal
neonatal dairy calves, levamisole can promote non-spe-
cific immune responses, although further studies using
more precise methodology will be necessary.
References
Asif MM, Zia-ul-Rahman Naqvi ZH (1995) Effect of levamisole
administered orally on haematological and biochemical profiles
of Sahiwal heifers. Vet Arch 65:185–192
Babiuk LA, Misra V (1981) Levamisole and bovine immunity: in
vitro and in vivo effects on immune responses to herpes virus
immunization. Can J Microbiol 27:1312–1319
Babiuk LA, Misra V (1982) Effect of levamisole in immune re-
sponses to bovine herpes virus I. Am J Vet Res 43:1349–1354
Bekere RY (1988) Effect of levamisole on formation of natural
immunity in neonatal calves, Teoreticheskie i Prakticheskie
Voprosy Veterinarii: Materialy Respublikanskoi Konferentsii
Dostizhenie Veterinarnoi Nauki i praktiki po povysheniyu
produktivnosti sel, vol 2, pp 40–42
Boothe DM (2001) Immunomodulators or biologic response
modifiers, introduction and miscellaneous agents. In: Boothe
DM (ed) Small animal clinical pharmacology and therapeutics.
Saunders, Philadelphia, pp 363–364
Cabaj W, Stankiewiez M, Jonas WE, Moore LG (1995) Levamisole
and its influence on the immune response of lambs. Vet Res
Commun 19:17–26
Courtney CH, Roberson EL (1995) Chemotherapy of parasitic
diseases. In: Adams HR (ed) Veterinary pharmacology and
therapeutics. Iowa State University Press, Ames, pp 900–904
Dacie JV, Lewis SM (1984) Practical haematology. Churchill
Livingston, Edinburgh, pp 22–49
Deshpande AR, Gujar MB, Bannalikar AS (1991) Passive transfer
of some immunological activities in newborn calves from lev-
amisole treated dams. Indian Vet J 68:614–620
Findly VL, Munday BL (2000) The immunomodulatory effects of
levamisole on the nonspecific immune system of Atlantic sal-
mon Salmo salar. J Fish Dis 23:369–378
Goranov K, Bonovska M (1987) Effect of levamisole on the
cytochemical function of leukocytes and on blood lysozyme in
sheep. Vet Med Nauki 24:72–76
Hogarth-Scott RS, Liardet DM, Morris PJ (1980) Levamisole
vaccine combinations: heightened antibody response. Aust Vet
J 56:285
Hunter KW, Fischer GW, Sayles PC, Strickland GT (1981) Lev-
amisole: potentiation of primary immunoglobulin M antibody
responses in suckling rats. Immunopharmacology 3:117–127
Irwin MR, Holmberg CA, Knight HD, Hjerpe CA (1976) Effects of
vaccination with infectious bovine rhinotracheitis and simulta-
neous administration of levamisole on primary humoral
responses in calves. Am J Vet Res 37:223–226
Ivanov IE, Arsov R, Dimov I, Sizov I (1987) Effect of tuberculin
and levamisole on the immune response after vaccinating calves
against para influenza and salmonella infections. Vet Med
Nauki 24:43–49
Jain NC (1986) Schalms veterinary hematology. Lea and Febiger,
Philadelphia, pp 66–67
Keskar DV, Venkataraman R, Srinivasan SR, Dhanapalan P
(1996) Prednisolone induced immunodeficiency in buffalo
calves and its correction with levamisole. Indian Vet J 73:102–
103
Kotowski K (1991) Wplyw wybranych preparatow na przebieg
okresu poporodowego u krow i na stan zdrowotny noworod-
kow. Med Weter 47: 123–125
Krakowski L, Krzyzanowski J, Wrona Z, Siwicki AK (1999) The
effect of nonspecific immunostimulation of pregnant mares with
1,3/1,6 glucan and levamisole on the immunoglobulins levels in
colostrum selected indices of nonspecific cellular and humoral
immunity in foals in neonatal and postnatal period. Vet
Immunol Immunopathol 68:1–11
Nalini-Kumari K, Choudhuri PC (1986) Effect of levamisole on the
haematological response of buffalo calves to rinderpest tissue
culture vaccine Kerala. J Vet Sci 17:90–95
Table 2 Mean ± SE of serum proteins measurements with statistical comparisons between trials groups
Timepoint Total protein(g/l) Beta globulin(g/l) Gamma globulin(g/l) A:G
Test Control Test Control Test Control Test Control
24–48 h 64.8±2.7 60.10±1.7 9.6±0.8 9.8±1.1 17.1±2.9 13.4±1.6 1.00±0.13 1.03±0.09
P value 0.15 0.74 0.3 0.74
First week 64.6±1.9 64.9±1.2 14.2±0.6 14.4±0.7 13.7±1.7 13.6±1.4 1.00±0.08 0.92±0.04
P value 0.91 0.79 0.97 0.41
Second week 63.2±1.4 61.8±1.1 10.8±0.9 10.1±0.6 12.5±1.9 11.9±0.9 0.99±0.08 1.00±0.03
P value 0.46 0.11 0.98 0.88
Third week 64.2±1.4 62.1±1.3 10.6±0.5 9.2±0.7 12.4±1.5 12.4±1.5 0.98±0.06 1.06±0.07
P value 0.26 0.09 0.87 0.47
Fourth week 63.6±1.7 61.6±0.8 9.6±0.3 9.8±0.4 16.1±1.6 10.7±0.5 0.85±0.05 0.96±0.06
P value 0.55 0.72 0.02 0.06
135
Ogunbiyi PO, Conlon PD, Black WD, Eyre P (1988) Levamisole
induced attenuation of alveolar macrophage dysfunction in
respiratory virus induced calves. Int J Immunopharmacol
10:377–385
Paulik S, Slanina L, Dubaj J, Boroskova Z, Benkova M, Szechenyi
S (1989) Vplyv krvneho derivatu s imunomodulatorom na
imunobielkovinovy profil u teliat v klinickych. Vet Med Praha
34:705–715
Paulik S, Svrcek S, Huska M, Mojzisova J, Durove A, Benisek Z
(1992) The effect of fungal and yeast glucan and levamisole on
the level of the cellular immune response in vivo and leukocyte
phagocytic activity in mice. Vet Med Praha 37: 675–685
Qureishi ZI, Lodhi LA, Jamil H, Nawaz M (2000) Effect of lev-
amisole hydrochloride on serum and colostral antibody titres
against foot and mouth disease virus in vaccinated buffaloes
(Bubalus bubalis). Vet Arch 70:59–66
Renoux G (1980) The general immunopharmacology of levamisole.
Drugs 20:89–99
Roth JA, Kaeberle ML (1984) Effect of levamisole on lymphocyte
blastogenesis and neutrophil function in dexamethasone-treated
cattle. Am J Vet Res 45:1781–1784
Sharma LK, Jagadish S, Mulbagal AN (1990) Effects of haemor-
rhagic septicemia vaccination and levamisole administration on
the humoral responses in cross bred calves. J Vet Pharmacol
Ther 13:23–28
Singh KC, Dhawedkar RG (1993) Immunomodulating effects of
levamisole in chicks immunocompromised by infectious bursal
disease virus. Trop Anim Health Prod 25:11–14
Singla LD, Juyal PD (1992) Immunomodulatory effects of lev-
amisole against Trypanosoma evansi infection in cow-calves
serum gammaglobulins. J Vet Parasitol 6:9–14
Sopinska A, Guz I (1993) Immunostymuljace dzialanie lewamizolu
i preparatu TFX-Polfa u warunkach eksperymentalnych. Med
Weter 49:547–550
Stogause A, King MG (1995) Is oral levamisole immunostimula-
tion in rats mediated by reduced levels of free plasma cortico-
sterone?. Int J Immunopharmacol 17:635–640
Szeto C, Gillespie KM, Mathieson PW (2000) Levamisole induces
interleukin 18 and shifts type 1/type 2 cytokine balances.
Immunology 100:217–224
Wawron W, Szczubial M (2000) Stymulacja ukladu odpornoscio-
wego krow i swin w okresie okeloporodowym. Med Weter
56:764–768
Wisniewski I, Grabowska G, Trybala E, Rotkiewcz Z (1993)
Wplyw podonia biotropiny i lewamizolu na wybrane wskazniki
odpornosci swoistej i nieswoistej u swin. Med Weter 49:66–68
Zia-ul-Rahman Z, Sandhu MA, Ahmad T (2003) Haematological
and serum biochemical profiles of buffalo heifers as influenced
by levamisole. Comp Clin Pathol 12:147–150
136
... In this study, the usage of levamisole increased the number of neutrophils before administrating anthrax vaccine for cattle. This increase in the number of neutrophils is consistent with the results reported by Mohri et al. (2005) and Bilandžić et al. (2010). In a study, it has been reported that PPR vaccine and levamisole administration to goat did not show any change in neutrophil count (Undiandeye et al. 2014), while in another study, neutrophil count decreased in sheep that received FMD vaccine (Rahman et al. 2002, Abdullah andBaşbuğan 2020). ...
... In the study, on the 7th and 14th days following the vaccine and drug administration, the number of monocytes in the levamisole-vaccine group increased compared with the vaccine group only. The results of the research are similar to those reported by Stelletta et al. (2004), Mohri et al. (2005), Undiandeye et al. (2014), Das et al. (2016), and Rao et al. (2017). It is thought that the increase in monocytes in the levamisolevaccine group could be due to the stimulating effect of levamisole on macrophages for antigens. ...
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Bu araştırmada şarbon hastalığına karşı aşılanan sığırlarda levamizol uygulamasının bağışıklık sistemi üzerine olan etkisi araştırıldı. Araştırmada toplam 40 adet sağlıklı sığır kullanıldı. Sığırlar dört eşit gruba ayrıldı. Kontrol grubuna üçer gün arayla ve bir dozu da 10. gün olmak üzere plasebo olarak serum fizyolojik dört defa deri altına enjekte edildi. İkinci gruba (aşı grubu) üçer gün arayla üç kez serum fizyolojik sonrası 10. gün şarbon aşısı deri altı, üçüncü gruba (aşı-levamizol) üçer gün arayla üç kez levamizol çözeltisinden 2.5 mg/kg dozda deri altı ve sonrası 10. gün şarbon aşısı deri altı, dördüncü gruba (levamizol) ise üçer gün arayla üç defa levamizol 2.5 mg/kg dozda deri altı ve sonrası 10. günde serum fizyolojik deri altına enjekte edildi. Aşılama sonrası aşı-levamizol grubunda nötrofil, lenfosit, monosit ve serum İgG miktarının sadece aşı uygulanan gruba göre anlamlı düzeyde (p
... Same effect was obtained by [11], these obtained results nearly agree with those observed by [34] who found an increased in total protein following levamisole treatment. Also, [12,14,22] found that levamisole caused an increase in immunoglobulin and immunity of the animals due to increase in globulin. On the other hand, the above mentioned results were also supported by the previous studies [13] mentioned that rats treated with levamisole show significant increase in total serum protein and globulin and such findings may be due to the ability the levamisole to enhance both cellular and humeral immune responses to restore depressed immune function through stimulating antibody formation and enhance T-cell response by stimulating T-cell activation and proliferation. ...
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In this study (20) ewes where examined and subdivided into two groups, the 1st group test group (n=10) where treated with Levamisole at dose 2.5 mg/kg while the 2nd group was untreated and considered control group (n=10) blood samples were collected into EDTA – containing tubes. Blood samples from all were continued at the day 0,7,14 and 21.The level of erythrocytes count, PCV, Hb, total leukocyte count, differential leukocytes count (manual standard method), total serum protein, albumin and globulin were measured to evaluate this study.Appropriate statistical methods were used for data analysis, and (P<0.05).was considered as significant. No significant differences were seen for PCV, RBCs, and Hb. Neutrophil level at day 14 and monocyte level at day 21 were significantly higher than in the control group (P<0.05).The results show insignificant increase in the total protein and Globulin and insignificant decrease in the albumin.leavamesole enhance nonspecific immune response due to induce leukocytosis, neutrophilia and monocytosis .
... The pro-inflammatory cytokines also stimulate immunoglobulin production (γ-globulin) and arrange acute phase response (α and β-globulin), leading to the outstanding hyperglobulinemia (and the subsequent hyperproteinemia and decreased A/G), hypoalbuminemia (negative acute phase reactant) and increased positive APPs (Fb, Hp, SAA, Cp) in levamisole and BCG groups along the research. Hyperglobulinemia, hypoalbuminemia, and acute phase response were recorded before with levamisole and BCG administrations by many authors (24,(27)(28)(29)(30)(31). In addition, the pro-inflammatory cytokines increase free radicals' formation and accumulation causing the oxidative stress noted in both groups (represented by the decreased TAC). ...
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Levamisole, BCG, vitamin E & Selenium are traditional immunopotentiating agents. This study aimed to monitor and compare between their effects on some clinicopathological and immunological parameters. For this purpose, sixty clinically-healthy 6-months Barki male lambs were equally divided into three groups: The first group was injected S/C with l ml of levapan ® 10% /50kg B.Wt (100 mg of levamisole) for 3 consecutive days, while the second group was injected S/C with 0.1 ml of BCG vaccine, and the third group was injected S/C for one time with E and Se 0.5 ml /10 kg B. Wt. Blood samples were collected at 0, 3, 7, 14, 21, and 35 days. Clinicopathological and immunological parameters were estimated and statistically analyzed. The three groups displayed a significant enhancement in the estimated immunological parameters (elevated neutrophils count, neutrophils phagocytic activity and index, globulin, and acute phase proteins), but the BCG group had the highest degree of immunopotentiating action for a longer time. The E and Se group and levamisole group were almost equal. On the other hand, the erthyrogram, total antioxidant capacity, liver and kidney functions with the BCG, and levamisole groups were negatively affected, while they were enhanced in the E and Se group for 14 days. In addition, the iron profile showed significant hypoferremia, hypotransferrinemia, and hyperferritinemia with the BCG group, and non-significant changes with both, the levamisole and E and Se groups. We concluded that the BCG has a powerful and sustainable immunomodulatory effect and it is recommended to inject it combined with E and Se to avoid its side effects.
... Phosphoramide, an alkylating agent generated by the bio-activation of cyclophosphamide could be responsible for the death of leucocytes as observed in the negative control [42]. Leucocyte count of the standard control was observed to be similar to the that of the normal control which demonstrated efficacy of Levamisole as an immune-booster [43]. This agrees with finding of Undiandeye et al. [44] who reported an increase in leucocyte count following treatment of an immunocompromised goat. ...
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Background Datura stramonium L. (Solanaceae) is used traditionally in west Africa to treat asthma, epilepsy, rheumatoid arthritis, filariasis microbial infections and conjunctivitis. This study investigated the immunomodulatory effects of aqueous seed extract of D. stramonium L. (ASEDS) on Wistar rats. Methods Thirty Wistar albino rats (180–200 g) were randomized into 6 groups (n = 5). Group 1 received distilled water only. Rats in groups 2–6 were pretreated with 10 mg/kg body weight (b.w.) Cyclophosphamide orally for 27-days to induce immunosuppression. Thereafter, they received treatment orally for 28 days as follows: Group 2 (distilled water), group 3 (5 mg/kg b.w. Levamisole), groups 4–6 (60, 90 and 120 mg/kg b.w. ASEDS, respectively). HPLC was used to determine major compounds in ASEDS. The effects of ASEDS on immune cells, immunoglobulins A, G and M levels, lipoproteins, and antioxidant status of rats were evaluated. Results ASEDS indicated high content of Acutumine, Quinine, Catechin, Chlorogenic acid, Gallic acid, Quercetin, Vanillic acid, Luteolin, Formosanin C, Saponin, Cyanidin, Tannic acid, 3-Carene, Limonene and α-terpineol. Cyclophosphamide triggered significant (p < 0.05) reduction in total leucocyte count and differentials, IgA, IgG, high-density lipoproteins (HDL), catalase, superoxide dismutase, glutathione peroxidase, vitamins A, C and E levels of untreated rats. Administration of ASEDS led to significant (p < 0.05) improvement in immune cell counts, immunoglobulin synthesis, high-density lipoprotein concentration, and antioxidant status of rats in the treated groups. Conclusions The results obtained from the study showed the immunomodulatory activity of ASEDS, thereby indicating its potential in immunostimulatory drug discovery.
... It is likely that parasitic control with levamisole from an early age in calves can interfere both in animal welfare, as well as in the stimulation of innate immunity (Pekmezci and Cakiroglu 2009). Reports have shown that levamisole can enhance the immunology responses and therefore improve the performance of production animals (Mohri et al. 2005). However, it has not been shown whether levamisole treatment can have a direct correlation between weight gain and its immunomodulatory effects in both rearing and adulthood in beef producing cattle. ...
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The aim of the present work was to study the effect of administration of levamisole on parasitic load of gastrointestinal nematodes (GIN) and the percentage of weight gain of grazing cattle. The animals were randomly distributed to form three experimental groups, levamisole, ivermectin and control. The collection of feces samples was carried out one day before and 15 days’ post-treatment and subsequently it was quantifying the eggs number per gram of feces. The body weight of the animals was recorded at days 0, 15, 30 and 45 after treatments to evaluate its gain. The results observed up to the final day (45 days’ post-treatment) showed the group treated with Ivermectin had a 10.1% increase in body weight, while the group under Levamisole treatment had an increase of 14.3%. The groups under ivermectin and levamisole showed a decrease in the number of eggs per grams of feces (EPG), which were measured 15 days after their treatment (22.5 EPG in ivermectin) and (55.0 EPG in levamisole) compared to the vehicle group (377.5 EPG) and pre-treatment (486.5 EPG). In the present work, it was possible to show that with two subcutaneous administrations of levamisole in grazing calves in the municipality of Chiltepec, Oaxaca, it’s possible to increase the weight in cattle while decreasing its parasite load of GIN. However, it is necessary to determine the anthelmintic resistance in farms that report the use of levamisole with different treatment and repeated doses of levamisole.
... Phosphoramide, an alkylating agent generated by the bio-activation of cyclophosphamide could be responsible for the death of leucocytes as observed in the negative control [30]. Leucocyte count of the standard control was observed to be similar to the that of the normal control which demonstrated e cacy of Levamisole as an immune-booster [31]. This agrees with nding of Undiandeye et al. [32] who reported an increase in leucocyte count following treatment of an immunocompromised goat. ...
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Background: Datura stramonium L. (Solanaceae) is used traditionally in West Africa to treat asthma, epilepsy, rheumatoid arthritis, filariasis microbial infections and conjunctivitis. This study investigated the immunomodulatory effects of aqueous seed extract of D. stramonium L. (ASEDS) on Wistar rats. Methods: Following phytochemical analysis of ASEDS and acute toxicity study, thirty Wistar rats of both sexes (180-200 g) were randomized into 6 groups (n = 5). Rats in groups 1, 2 and 3 served as normal, negative and standard controls respectively. Immunosuppression was induced using Cyclophosphamide, 10 mg/kg body weight (b.w.) orally for 27 days. Group 2 rats were untreated while Groups 3-6 rats received 5 mg/kg b.w. Levamisole, 60, 90 and 120 mg/kg b.w. ASEDS orally for 28 days respectively. The effects of ASEDS on immune cells, immunoglobulins A, G and M levels, lipoproteins, and antioxidant status of immunosuppressed rats were evaluated. Results: ASEDS indicated LD50 above 5000 mg/kg b.w. with moderate contents of carbohydrates, glycosides, saponins, tannins, terpenoids, and high contents of alkaloids, flavonoids and phenols. Cyclophosphamide triggered significant (p < 0.05) reduction in total leucocyte count and differentials, IgA, IgG, high-density lipoproteins (HDL), catalase, superoxide dismutase, glutathione peroxidase, vitamins A, C and E levels of the negative control rats. Treatment with ASEDS led to significant (p < 0.05) increases in immune cell counts, immunoglobulin synthesis, HDL levels, and antioxidant status of the test groups. Conclusions: The findings demonstrate the immunomodulatory benefits of ASEDS and its potential in the development of potent immunomodulatory drugs.
... Same effect was obtained by [11], these obtained results nearly agree with those observed by [34] who found an increased in total protein following levamisole treatment. Also, [12,14,22] found that levamisole caused an increase in immunoglobulin and immunity of the animals due to increase in globulin. On the other hand, the above mentioned results were also supported by the previous studies [13] mentioned that rats treated with levamisole show significant increase in total serum protein and globulin and such findings may be due to the ability the levamisole to enhance both cellular and humeral immune responses to restore depressed immune function through stimulating antibody formation and enhance T-cell response by stimulating T-cell activation and proliferation. ...
Article
This study conducted a literature review to investigate the immunomodulatory effect of levamisole in both humans and farm animals. The following procedure was followed for database searching: PubMed, Google Scholar, Web of Science, and Cochrane Library. All research works were updated to September 2022. The terms used in the literature search were included: (“levamisole” OR “immunity” OR “immune system”) AND (“adjuvant” OR “fish” OR “poultry” OR “farm animal” OR “cattle” OR “sheep”). The current review enlightens the extensive potential of levamisole as an adjuvant immunotherapeutic agent and explains its divergent applications beyond its antiparasitic use as an adjuvant, dietary supplement, immunostimulant, antiviral, and anti-cancer drug in humans and farm animals. In the articles examined, various mechanisms have been proposed for levamisole immunoprotective effects, but hormonal alteration and stress hormone reduction are indicated as the main mechanisms in various animal species.
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Objective This study aimed to evaluate a new drug combination for small ruminant respiratory diseases to find a better treatment protocol for the potential replacement of older methods. Materials and Methods A total of 6,886 animals received common respiratory disease therapies out of 15,845 animals that had respiratory disorders. The new combination therapy technique treated the remaining animals (8,968). The animals were given an oral suspension of triclabendazole or levamisole at an initial dosage of 0.2 ml/kg body weight (BW). The following day, 0.2 mg/kg of 1% ivermectin was subcutaneously administered. Then, on the third and fifth days of treatment, a subcutaneous injection of 30 mg/kg BW of florfenicol (30%) was administered. The survival and recovery rates for both groups were tracked throughout a 6-month period of observation. Postmortem and histopathological signs were also assessed. Results In the group of the novel combination therapy, group A, clinical, postmortem, and histopathological signs were significantly reduced compared to group B. Clinical signs and mortality in group A were 90% and 93% lower than in group B, respectively. Animals that received the new combination therapy were healed of their disease and stayed immune for 6 months. Conclusion This novel therapy demonstrated significant efficacy against respiratory diseases in a 10-year field study. The paper proved that the protocol introduced could be a new therapeutic approach.
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In this study, the effect of used immunostimulating drugs with FMD vaccine on immunoglobulins was aimed to investigate in sheep. For this purpose 40 healthy sheep were divided into 4 groups. Blood and serum samples were taken from all animals from 0 days before the study. Blood samples were measured immediately, and IgA, IgG, IgM, IgE and Zn values from biochemical parameters were stored for measurement. Group I was applied only FMD vaccine, group II Levamisole with the FMD vaccine, group III Zinc with FMD vaccine and the last group IV AD3E was applied with FMD vaccine. After 21 days, blood and serum samples from all groups were taken again and hematologic and IgA, IgG, IgM, IgE and Zn values were compared according to the values of day 0. No statistical difference was found between the groups except for PLT in hematological parameters (p> 0, 05) when compared to pre-vaccination and post-vaccination. In groups II and III there was a significant increase in PLT levels. Biochemical analysis showed IgA, IgG, IgM and IgE levels to be higher in IgG (p <0, 05) and IgE (p <0,001) in groups II and III when levels compared to before vaccination. There were statistically significant increases in IgM (p <0.05) in group IV.
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QURESHI, Z. I., L. A. LODHI ,H. J AMIL ,M. N AWAZ: Effect of levamisole hydrochloride on serum and colostral antibody titres against foot and mouth disease virus in vaccinated buffaloes (Bubalus bubalis). Vet. arhiv 70, 59-66, 2000. ABSTRACT A study was conducted to ascertain whether post-vaccination antibody titres in serum and colostrum against foot and mouth disease virus in pregnant buffaloes (Bubalus bubalis) could be enhanced by simultaneous administration of levamisole hydrochloride. Twenty-four pregnant buffaloes were divided into three groups of equal size: unvaccinated, vaccinated control, and levamisole-treated vaccinated. The vaccination was given 10 weeks prior to expected parturition. Weekly serum samples were collected until parturition, while colostrum samples were obtained within 1h after parturition. Passive haemagglutination test was applied to determine antibody titres. Levamisole-treated animals showed a progressive rise in antibody titre until week 6, reaching a peak value of 70.0 ± 4.3 (SD) during that same week. Levamisole hydrochloride significantly (P
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Diseases having a multifarious etiology, both infectious and non-infectious, together with unfavorable environmental agents are becoming increasingly important in intensive stock and swine breeding. This issue is particularly important in the case of pregnant females. Stress caused by improper upkeep, feeding and the labour itself may result in immuno-suppression and finally in post-natal disorders. And although chemotherapy still remains the treatment of choice in prenatal infectious diseases, drugs that stimulate the immune system of females are more and more commonly used. The drugs presently available on the market may be divided into natural - derived from bacteria, viral, vegetal, hormonal and synthetic. The natural immunomodulators include: anaerobic Corynebacterium (Propionibacetrium), BCG, lipopolysaccharides, Lidium KLP, Parapoxovirus ovis D 1707-Baypamun P. In addition, Bacillus subtilis, Corynebacterium uberis, Mycobacterium chelonae and glucan are used. The synthetic immunostimulators include: levamisole, nitrogranulogen, imutiol, isoprynosine, asymekson and pirydoksyne. Homeopathic drugs also stimulate the immune system in the prenatal period. The present paper discusses the mechanisms of action of the individual immunostimulants and their effectiveness in the treatment of postnatal disorders in cows and pigs.
Article
Levamisole was combined with a clostridial vaccine and experiments conducted in sheep to determine the effect on anthelminitic and vaccine efficacy. Vaccine potency was assessed in separate experiments in 200 sheep (divided into 5 groups). The individuals in each group were injected with one of the following 5 different preparations: levamisole combined with anaerobic vaccine at a pH of either 3.5 or 6.0, vaccine alone at a pH of either 3.5 or 6.0, and levamisole alone. The combined levamisole / vaccine preparations had been stored for not less than 6 months prior to testing. A statistically-significant heightened antibody response to 5 antigenic components in the vaccine was obtained when the pH of the vaccine was reduced to 3.5 and the vaccine was given in combination with levamisole. This trend was present in the antibody response of the sheep when a pooled sample of the individual serums was tested at 6 weeks, 8 weeks and 14 weeks (8 weeks after the second injection). From the analysis of the individual serums at week 8 (2 weeks after the 2nd injection) there was evidence that the distribution curve of the litres had shifted to the right suggesting that the zero or poor responders in the population had improved immunocompetence, with the better responders also improving proportionately. The immunogenicity of the blackleg component was tested in sheep, 9 weeks and 32 weeks after the second injection and gave complete protection to a lethal challenge of Clostridium chauvoei. This combination offers not only increased ease of administration by providing a single anthelmintic and anaerobic vaccines injectable preparation (probably treatment with either or both is the two most common and important veterinary procedures undertaken by farmers, but in addition, the antibody titre of the treated animals is significantly increased. Part 2 of this paper establishes that the anthelmintic efficacy of the levamisole / vaccine combination was not impaired and that tissue reactions at the site of injection were acceptable.
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Sea water-adapted Atlantic salmon, Salmo salar L., were given a 2-h bath in a 2.5 mg L−1 levamisole (as levamisole hydrochloride) solution in fresh-water. Following bathing, the fish were held in full salinity sea water for 2 weeks before being subjected to a number of immunological assays. Heightened activity of the nonspecific defence system was demonstrated by increases in phagocytic index, phagocytic capacity and phagocytic activity, increased levels of the reactive oxygen intermediate, superoxide anion, and an increased lytic activity of both the mucus and the serum. These results indicate that levamisole is effective in augmenting parts of the nonspecific defence system of Atlantic salmon. This is the first record of the use and efficacy of levamisole as an immunomodulator in Atlantic salmon.
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Serum was separated from blood samples of six healthy buffalo heifers (1–1.5 years) on day 0 (control) and after 1, 7 and 14 days of levamisole (15 mg/kg body weight) administered orally. Significant differences were observed among monocytes, ESR (1 h) and of percentage PCV (Packed Cell Volume) after 1 and 7 days of levamisole administration. Mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) were significantly different. Significant changes were observed among total serum protein, albumin and globulin concentrations after 1 and 7 days of levamisole administration. A significant increase in serum urea concentration was observed on day 14 of the experiment.
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The objectives of the studies were to evaluate the effect of levamisole and 1,3/1,6 glucan applied in pregnant mares on parameters of non-specific cellular and humoral immunity of foals. Eighteen mares in three experimental groups (six animals in each) and their progeny were examined. Multiparous mares, crossbreed of Polish, full-blood and Hannover lines (400–500 kg), 4–9 years old, originated from four different farms. They were kept under identical zoohygienic and nutritional conditions. The animals were randomly chosen in experimental groups. None of mares had been previously vaccinated. In group I, levamisole was injected three times at 7-day intervals at a dose of 2.5 mg/kg of body weight. Group II was injected at the same periods of time and manner with 1,3/1,6 glucan at a dose of 0.19 mg/kg of body weight, whereas mares in group III served as controls. Injection of the immunostimulators started in mares 4–6 weeks before expected parturition. Blood was taken from foals before the first dose of colostrum, then 18 and 36 h after the first dose of colostrum and on Days 7, 14, 21, 28, 35, 42, 49 and 56 of life. The parameters determined in blood were reduction of NBT by PMNs, phagocytic activity, phagocytic index, test of intracellular killing and in blood sera were total protein, γ-globulin fraction, lysozyme activity, level of IgG, IgG(T), IgM and IgA. In the first dose of colostrum taken just after parturition, specific gravity, total protein, γ-globulin complex, lysozyme activity, level of IgG, IgG(T), IgM, IgA were determined. Colostrum of mares immunostimulated with levamisole or 1,3/1,6 glucan were characterized by a high content of IgG and IgG(T) compared to the colostrum of nonstimulated mares. The level of immunity was higher in foals from dams immunostimulated with levamisole or 1,3/1,6 glucan. Clinical examinations in neonatal and postnatal period did not show any abnormalities in these foals